2. Academic Validation
  3. Tanshinone IIA derivatives inhibits colorectal cancer growth by targeting pyruvate kinase M2

Tanshinone IIA derivatives inhibits colorectal cancer growth by targeting pyruvate kinase M2

  • Eur J Med Chem. 2025 Dec 13:305:118477. doi: 10.1016/j.ejmech.2025.118477.
Jing Bai 1,  Shengli Liu 1,  Zhiguo Mang 2,  Xueqing Duan 1,  Changfeng Song 3,  Weiyi Tian 4
Affiliations

Affiliations

  • 1 Guizhou Key Laboratory of Microbial and Infectious Disease Prevention & Control, School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, People's Republic of China.
  • 2 Guizhou Yaofa Natural Medicine Technology Co., Ltd, Guiyang, 550025, People's Republic of China.
  • 3 Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Fudan University, Shanghai, 201399, People's Republic of China. Electronic address: songcf2013@126.com.
  • 4 Guizhou Key Laboratory of Microbial and Infectious Disease Prevention & Control, School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, People's Republic of China. Electronic address: tianweiyi@gzy.edu.cn.
PMID: 41512539 DOI: 10.1016/j.ejmech.2025.118477
Abstract

Pyruvate Kinase M2 (PKM2), a key glycolytic enzyme, is frequently overexpressed in colorectal Cancer (CRC) and has emerged as a promising therapeutic target. In this study, a series of Tanshinone IIA derivatives were designed and synthesized through simultaneous modification of rings A and D, and their anti-CRC activities were evaluated. The optimized derivative 23 exhibited PKM2 activation (AC50 = 92.12 nM) and significantly inhibited the proliferation of CRC cells. Molecular docking analysis revealed that the piperidinothiophene moiety in 23 strengthens binding through a salt bridge interaction with Asp295. Furthermore, 23 suppressed the PKM2/STAT3 signaling pathway both in vitro and in vivo. Together, these findings highlight derivative 23 as a promising Anticancer candidate for the treatment of CRC.

Keywords

Colorectal cancer (CRC); Pyruvate kinase M2 (PKM2); STAT3 signaling pathway; Tanshinone IIA (Tan IIA); Warburg effect.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z